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Cucurbitacin B (Cu B),a potent anti-cancer agents,suffers with the problems of gastrointestinal side effects and non-specific toxicity via oral administration and drawbacks in patients compliance and acceptance through injections.An integration of nanoscopic carriers with mucoadhesive buccal films drug delivery system would resolve these issues effectively with greater therapeutic benefits and clinical significance.Thus,the drug loaded mucoadhesive buccal film was developed and characterized in this study and the carboxymethyl chitosan (CCS) was choosed as a bioadhesive polymer,glycerol was choosed as a plasticizer and phospholipid-bile salts-mixed micelles (PL-BS-MMs) was selected as the nanoscopic carriers.The CCS-films containing Cu B loaded PL/SDC-MMs was evaluted for the mechanical properties,mucoadhesion properties,in vitro water-uptake,in vitro release and morphological properties,respectively.The optimal CCS-films containing Cu B loaded PL/SDC-MMs was easily reconstituted in a transparent and clear solution giving back a colloidal system with spherical micelles in the submicron range and presenting the good characteristics after reconstituting into micelles solution compared with corresponding results of initial Cu B-PL/SDC-MMs solution.The in vivo study revealed a greater and more extended release of Cu B from nanoscopic CCS-films compared to that from a conventional CCS films (C-CCS-films) and oral marketed tablet (Hulusupian).The AUC0-36h for CCS-films containing Cu B loaded PL/SDC-MMs was found to be 46.43±5.11 μg/mL/h in comparison to 4.44±1.21 μg/mL/h and 17.23±3.46 μg/mL/h for C-CCS-films and oral tablet,respectively.The absorption of Cu B from CCS-films containing Cu B loaded PL/SDC-MMs resulted in 2.69-fold increased in bioavailability as compared to conventional tablet formulation and 10.46 times with reference to the C-CCS-films formulation.Thus,this kind of mucoadhesive buccal film might be an alternative safe route for delivery of Cu B avoiding gastrointestinal side effects and non-specific toxicity with better patient compliance and higher bioavailability for the treatments.